Hydrogen sulfide mitigates ox‑LDL‑induced NLRP3/caspase‑1/GSDMD dependent macrophage pyroptosis by S‑sulfhydrating caspase‑1

作者：Zhenli Jia, Xulin Zhang, Zhiyi Li, Hanyu Yan, Xiangqin Tian, Chenghua Luo, Ketao Ma, Ling Li, Liang Zhang · 发表于：Molecular Medicine Reports · 年份：2024 · DOI：10.3892/mmr.2024.13259 · 被引用次数：22 · 研究领域：Sulfur Compounds in Biology、Eicosanoids and Hypertension Pharmacology、Heme Oxygenase-1 and Carbon Monoxide

Macrophage pyroptosis mediates vascular inflammation and atherosclerosis (AS). Hydrogen sulfide (H2S) exerts a protective role in preventing inflammation and AS. However, its molecular mechanisms of regulating the pyroptosis signaling pathway and inhibiting macrophage pyroptosis remain unexplored. The present study aimed to determine whether H2S mitigates macrophage pyroptosis by downregulating the pyroptosis signaling pathway and S‑sulfhydrating caspase‑1 under the stimulation of oxidized low‑density lipoprotein (ox‑LDL), a pro‑atherosclerotic factor. Macrophages derived from THP‑1 monocytes were pre‑treated using exogenous H 2 S donors sodium hydrosulfide (NaHS) and D,L‑propargylglycine (PAG), a pharmacological inhibitor of endogenous H 2 S‑producing enzymes, alone or in combination. Subsequently, cells were stimulated with ox‑LDL or the desulfhydration reagent dithiothreitol (DTT) in the presence or absence of NaHS and/or PAG. Following treatment, the levels of H 2 S in THP‑1 derived macrophages were measured by a methylene blue colorimetric assay. The pyroptotic phenotype of THP‑1 cells was observed and evaluated by light microscopy, Hoechst 33342/propidium iodide fluorescent staining and lactate dehydrogenase (LDH) release assay. Caspase‑1 activity in THP‑1 cells was assayed by caspase‑1 activity assay kit. Immunofluorescence staining was used to assess the accumulation of active caspase‑1. Western blotting and ELISA were performed to determine the expression of pyroptos...